The Massachusetts (MA) Center for Birth Defects Research and Prevention (MCBDRP) proposes to continue its strong track record of conducting etiologic research to identify modifiable risk factors for structural birth defects through its participation in the Birth Defects Study to Evaluate Pregnancy exposureS (BD-STEPS). We will enhance our contributions by leveraging our already established training program designed to produce future birth defects researchers. MCBDRP brings to BD-STEPS our expertise and leadership in pharmacoepidemiology and collaborative utilization of unique data resources to be applied to all four key areas named in the Funding Opportunity Announcement. Our research will utilize existing data from the National Birth Defects Prevention Study, data to be collected as part of BD-STEPS and data sets unique to our collaborative team including the Pregnancy to Early Life Longitudinal database, the MA Outcomes Study of Assisted Reproductive Technologies, the Slone Epidemiology Center's multi-site Birth Defects Study, and the North American Antiepileptic Drug Pregnancy Registry. MCBDRP investigators are committed and successful mentors and collaborative partners, roles that will continue and expand within BD-STEPS. Over the five year grant period, the MCBDRP will complete at least 10 etiologic research projects that cover medically significant and common exposures as they relate to risks of birth defects including: 1) Oral diabetic medications, more common as the prevalence of diabetes increases; 2) Anti-obesity medications, which given the current increase in obesity have been and will continue to be approved by FDA; 3) Medications and procedures to treat infertility, an area where MA offers unique strengths due to the large number of older mothers and high utilization of assisted reproductive technology (ART); 4) Medications that contain the endocrine-disruptor phthalates, which will be a model for proposing to study additional inactive ingredients in medications; 5) Antiepileptic medications including the study of genetic factors which increase the risk for birth defects; 6) Non- steroidal anti-inflammatory drugs, important because they are used by more than 20% of pregnant women; 7) Drugs for nausea and vomiting of pregnancy, key because of the increasing use of some medications for this pregnancy-specific condition; 8) Spatio-temporal clustering of birth defects, an indication of environmental or infectious etiology, including an expansion of our work on gastroschisis and extension of the research methodology to other birth defects; 9) Antidepressants, specifically selective serotonin reuptake inhibitors, including effect modifiers and genetically determined predictors related to specific agents; and 10) Medications taken during pregnancy, including over-the-counter products, and through a periodic screening of BD-STEPS data, identifying new products that may pose a risk. Through these activities, MCBDRP will be an essential partner in BD-STEPS to achieve our overall goal of translating research findings into meaningful prevention initiatives.